Amphotericin B is one of the oldest antifungal medicines still used in specialist care. It remains important because it works differently from azole antifungals such as itraconazole, voriconazole, posaconazole and isavuconazole.
Resistance to azole antifungals is an increasing clinical concern in aspergillosis. Amphotericin B resistance can occur, but it is much less commonly encountered in routine patient care.
For most people with aspergillosis, this research is not a reason to worry that amphotericin B will fail if it is needed. Instead, recent research is helping scientists understand how amphotericin B resistance develops and how this valuable treatment might be protected or improved for the future.
What is amphotericin B?
Amphotericin B is an antifungal medicine that damages the fungal cell membrane. It binds to ergosterol, an important component of that membrane, causing damage that can lead to fungal cell death.
It is available in different formulations, including liposomal amphotericin B. It may be used for serious or invasive fungal infections, particularly when azole treatment is unsuitable, ineffective or affected by resistance.
Amphotericin B is valuable partly because it attacks fungi in a different way from the azoles. More information about antifungal treatment is available in our guide to the management of aspergillosis.
What did the original study find?
The original article on this website described a 2019 study from Brazil. Researchers tested 228 Aspergillus isolates and found that 27% of the Aspergillus fumigatus isolates tested showed reduced susceptibility or resistance to amphotericin B.
This was an important warning, but the figure needs careful interpretation. It did not mean that 27% of patients with aspergillosis had amphotericin B-resistant infections. The isolates came from a particular study population and cannot be used to estimate the risk for all patients.
Laboratory resistance results also do not always translate directly into treatment failure. The species of Aspergillus, the type of infection, the patient’s immune system, the drug formulation and the laboratory method used for susceptibility testing all matter.
How is this different from azole resistance?
Azole resistance is currently the more important resistance problem in clinical aspergillosis.
Azole resistance may develop during long-term treatment, but resistant Aspergillus strains can also be acquired from the environment. When resistance is suspected, it can make treatment more difficult because azoles are commonly used for several forms of aspergillosis.
Amphotericin B resistance is less commonly encountered in clinical practice. It remains an important alternative in some situations because it has a different mechanism of action.
That difference is valuable. If resistance to one antifungal class develops, another class may still be effective. Treatment decisions are made by specialist teams using the patient’s clinical condition, laboratory results and response to treatment.
New research is explaining how resistance works
Recent laboratory research is beginning to identify possible mechanisms behind amphotericin B resistance.
A 2024 study of A. fumigatus found that exposure to amphotericin B affected proteins involved in membrane transport, lipid handling and fungal metabolism. One protein, called RtaA, appeared to influence the movement or organisation of sterols within the fungal cell. Changes involving RtaA altered the fungus’s sensitivity to amphotericin B.
This does not mean that RtaA testing is currently available for patients. The finding is experimental. Its importance is that it gives researchers a possible biological pathway to investigate when developing new treatments or resistance tests.
Read the study on RtaA and amphotericin B resistance.
A separate 2025 study examined Aspergillus terreus. This species is already known to have naturally reduced susceptibility to amphotericin B. The researchers found that changes in fungal growth and genetic activity could alter amphotericin B susceptibility, highlighting how complicated resistance can be within a single species.
Read the study of Aspergillus terreus and amphotericin B susceptibility.
Why does species identification matter?
Not all Aspergillus species respond to antifungal medicines in the same way.
Some non-fumigatus Aspergillus species may have higher amphotericin B minimum inhibitory concentrations in laboratory testing. However, interpreting these results is difficult because clinical breakpoints are not available for every species, and studies may use different laboratory methods.
This is one reason specialist laboratories and clinical teams need to interpret susceptibility results in context. A laboratory result is not, by itself, a prediction of what will happen to an individual patient.
Could newer medicines preserve the benefits of amphotericin B?
Researchers are also developing newer polyene antifungals. Polyenes are the drug family that includes amphotericin B.
One example is SF001, an experimental next-generation polyene. Laboratory studies suggest that it may retain broad antifungal activity, including activity against some amphotericin B-resistant isolates, while potentially causing less toxicity.
SF001 is not yet a routine treatment and requires further development and clinical testing. However, this research illustrates how understanding resistance mechanisms may help scientists develop safer and more effective medicines for the future.
Read the study of SF001 and amphotericin B.
What does this mean for patients?
For most people living with aspergillosis:
- amphotericin B resistance is not a common everyday concern;
- azole resistance is currently the more important clinical resistance problem;
- a laboratory finding of reduced susceptibility does not automatically mean treatment will fail;
- species identification and specialist interpretation are important;
- treatment decisions depend on the type of aspergillosis, the patient’s health, drug levels, side effects and laboratory results.
Patients receiving long-term azole treatment may need regular monitoring of symptoms, blood tests, liver function and antifungal drug levels. This is known as therapeutic drug monitoring and can help clinicians judge whether treatment exposure is adequate and whether side effects are developing. See our information about antifungal monitoring and therapeutic drug monitoring.
Protecting an important treatment for the future
Recent research is moving beyond simply detecting resistance. Scientists are beginning to understand the biology behind amphotericin B resistance and are using that knowledge to explore new and potentially safer antifungal medicines.
Amphotericin B resistance is not currently the same kind of widespread clinical problem as azole resistance. For most patients, this research is not a reason to expect treatment failure.
Its importance is that amphotericin B remains a valuable antifungal option, and research into resistance may help preserve or improve the polyene medicines available to patients with serious fungal infections in the future.
References
- Abou-Kandil et al. The proteomic response of Aspergillus fumigatus to amphotericin B reveals the involvement of the RTA-like protein RtaA in AmB resistance. MicroLife.
- Eisele et al. Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism. mBio. 2025.
- Vahedi-Shahandashti and Lass-Flörl. In vitro activity of SF001: a next-generation polyene versus amphotericin B. Antimicrobial Agents and Chemotherapy. 2025.
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